OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Objective:To analyze the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021.Methods:Herpes zoster cases were collected from a surveillance system in Beijing City from December 2017 to April 2021. The cases included individuals under 20 years old from seven sentinel hospitals located in two districts (Miyun District and Changping District). The basic information, the rash date of rash onset and the location and number of lesions were investigated at the first visit to the hospital, and the lesion swab samples were collected for laboratory testing. A telephone follow-up was conducted 21 days after the onset of the rash to investigate the degree of pain, duration of the rash and duration of pain. The individuals who still experienced neuralgia were further investigated for their pain condition at 90 days after the onset of the rash, to discover cases with postherpetic neuralgia. DNA was extracted from the rash fluid, and the ORF62 gene region was amplified and sequenced to obtain the viral sequence. The wild-type strain or chickenpox vaccine strain was identified by using sequence alignment, and the clinical characteristics of cases with different varicella vaccinations were compared.Results:A total of 78 herpes zoster cases under 20 years old were investigated during 2017-2021 in Beijing City, and 61 cases completed the follow-up survey. The age range of 61 cases was 1.83 to 20.54 years with a median age of 17.50 years. There were 36 males (59.02%) and 25 females (40.98%). Among them, there were 29 cases with the chickenpox vaccine immunization history (18 cases with one dose, 5 cases with two doses and 6 cases with unknown doses), 13 cases with no vaccination history and 19 cases with unknown vaccination history. Among the 78 cases, the herpetic fluid samples of 64 cases were positive for VZV, including 62 cases identified as wild-type strains and two cases as vaccine strains. The two vaccine strain cases were both 2-year-old girls who had received one dose of varicella vaccine and developed herpes zoster 3 months and 13 months after vaccination. Among the 29 cases with chickenpox vaccine immunization history, the majority had 10 to 49 lesions, accounting for 58.62% (17 cases). The trunk was the most common site of lesions, accounting for 44.83% (13 cases). About 51.72% (15 cases) reported "no or mild" pain intensity. The median ( Q1, Q3) scores for the worst pain, duration of pain and the time to crusting of lesions in the herpes zoster cases were 3 (1.5, 5) points, 10 (1.5, 12.5) days and 10 (6.5, 13) days, respectively. There was no statistically significant difference in the constituent ratio of the location of lesions, number of lesions and pain degree among the cases with vaccination history, without vaccination history and with unknown vaccination history ( P>0.05). There was also no statistically significant difference in the distribution of pain score, duration of lesions and duration of pain across the three groups ( P>0.05). Conclusion:Wild strains are the predominant pathogens in herpes zoster cases under 20 years old in Beijing City during 2017-2021. The varicella vaccination has no significant impact on the clinical manifestations of herpes zoster cases.

Objective:To investigate the epidemiological and clinical characteristics of RSV among patients aged ≥60 years in Beijing from 2015 to 2023.Methods:Based on the respiratory pathogen surveillance system, samples of upper respiratory tract infections (URTI), non-severe community-acquired pneumonia (nsCAP) and severe community-acquired pneumonia (sCAP) among people aged ≥60 years were collected from 28 sentinel hospitals in 16 districts of Beijing from January 2015 to December 2023. Swab samples were collected from URTI within one week, and lower respiratory tract samples from nsCAP and sCAP were collected. Demographic and epidemiological data were also collected. Various respiratory pathogens including RSV were detected.Results:From January 2015 to December 2023, a total of 20 349 cases of acute respiratory infections aged ≥60 years were included, with the RSV-positive rate of 1.54% (313/20 349, 95% CI: 1.39%-1.68%). Among them, the total RSV-positive rates of older people during the pre-pandemic, pandemic, and post-pandemic periods of COVID-19 were 1.59% (207/13 006, 95% CI: 1.38%-1.81%), 0.82% (38/4 650, 95% CI: 0.56%-1.08%) and 2.53% (68/2 693, 95% CI: 1.93%-3.12%), respectively. The difference in RSV-positive rate was statistically significant ( P<0.001). Based on the sampling time of cases, the RSV epidemic season for older people in Beijing was from October to March of the following year, with a peak period in December or January of the following year. In the post COVID-19 pandemic, there were very few RSV-positive cases detected in the elderly from April to June 2023, with only one positive case detected in May and one in June. The RSV-positive rate of older people increased significantly from October to December, reaching 11.75% (51/383) in December. Among 263 RSV-positive cases in the elderly, RSV-A, RSV-B and unclassified type accounted for 43.35% (114/263), 29.28% (77/263) and 27.38% (72/263), respectively. Since 2020, there has been a subtype conversion, with RSV-B being the main focus. Among 197 elderly cases that have complete clinical data, the main symptoms were cough (86.8%, 171/197), sputum (80.2%, 158/197) and fever (73.60%, 145/197). About 24.87% (49/197) of elderly cases experienced complications. The hospitalization mortality rate was 4.57% (9/197), and the hospitalization rate was 78.68% (155/197). The ICU occupancy rate was 1.99% (36/197). The mechanical ventilation usage rate was 13.32% (33/197), and the length of hospital stay [ M ( Q1, Q3)] was 12 (9, 16) days. Conclusion:In Beijing, the RSV infection rate is relatively low during the COVID-19 pandemic, and the prevalence of COVID-19 is relatively high. In 2023, there was no out-of-season outbreak of RSV infection among the elderly. Elderly RSV infection cases have multiple complications, severe diseases, and poor prognosis.

Objective:To compare the effects of unilateral thoracic paravertebal block with lidocaine on hemodynamic and the level of consciousness during double lumen endotracheal intubation.Methods:From June to october 2021,a total of 40 patients American Society of Anesthesiologists(ASA)physical status Ⅰ-Ⅱ,aged 19-65 years,scheduled for elective thoracic sugeries in Peking University Interna-tional Hospital block with under general anesthesia requiring orotracheal intubation were recruited and di-vided into two groups:The double-lumen endobronchial intubation(group C)and double-lumen endo-bronchial intubation after thoracic paravertebal block with lidocaine(group P).After an intravenous an-esthetic induction,the orotracheal double-lumen intubation was performed using a Macintosh direct laryn-goscopy,respectively.Invasive blood pressure(BP)and heart rate(HR)were recorded before and after anesthetic induction,immediately after intubation and 5 min after intubation with 1-minute interval and the intubation time was also noted.Rate-pressure product(RPP)were calculated.Results:After anes-thetic induction,BP and RPP in the two groups decreased significantly compared with their preinduction values.As comparison with their postinduction values,the orotracheal intubation in the two groups caused significant increases in BP,HR and RPP.Diastolic blood pressure(DBP)and mean arterial pressure(MAP)increased significantly and lasted for 1-minute in group C compared with the baseline values.Systolic blood pressure(SBP)was not significant change and DBP increased significantly immediately af-ter intubation in group P.HR of both groups after intubation were significantly higher than their baseline values and lasted for 4 min in group C,HR increased significantly immediately after intubation in group P.SBP,DBP,MAP,HR and RPP after intubation in group P were significantly lower than those of group C during the observation period.The value of BIS was similar between the two groups.Compared with group C,the incidence of SBP greater than 30％and RPP greater than 22 000 was significantly lower in group P in the observation period,and no patient in group P developed RPP greater than 22 000.At the end of the incidence of SBP less than 30％of the basal value and HR less than 30％of the baseline,no severe bradycardia occurred in both groups.Conclusion:During double-lumen endobronchial intubation,unilateral thoracic paravertebal block with lidocaine can provide less hemodynamic response and level of conscionsness.

Objective:To analyze the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021.Methods:Herpes zoster cases were collected from a surveillance system in Beijing City from December 2017 to April 2021. The cases included individuals under 20 years old from seven sentinel hospitals located in two districts (Miyun District and Changping District). The basic information, the rash date of rash onset and the location and number of lesions were investigated at the first visit to the hospital, and the lesion swab samples were collected for laboratory testing. A telephone follow-up was conducted 21 days after the onset of the rash to investigate the degree of pain, duration of the rash and duration of pain. The individuals who still experienced neuralgia were further investigated for their pain condition at 90 days after the onset of the rash, to discover cases with postherpetic neuralgia. DNA was extracted from the rash fluid, and the ORF62 gene region was amplified and sequenced to obtain the viral sequence. The wild-type strain or chickenpox vaccine strain was identified by using sequence alignment, and the clinical characteristics of cases with different varicella vaccinations were compared.Results:A total of 78 herpes zoster cases under 20 years old were investigated during 2017-2021 in Beijing City, and 61 cases completed the follow-up survey. The age range of 61 cases was 1.83 to 20.54 years with a median age of 17.50 years. There were 36 males (59.02%) and 25 females (40.98%). Among them, there were 29 cases with the chickenpox vaccine immunization history (18 cases with one dose, 5 cases with two doses and 6 cases with unknown doses), 13 cases with no vaccination history and 19 cases with unknown vaccination history. Among the 78 cases, the herpetic fluid samples of 64 cases were positive for VZV, including 62 cases identified as wild-type strains and two cases as vaccine strains. The two vaccine strain cases were both 2-year-old girls who had received one dose of varicella vaccine and developed herpes zoster 3 months and 13 months after vaccination. Among the 29 cases with chickenpox vaccine immunization history, the majority had 10 to 49 lesions, accounting for 58.62% (17 cases). The trunk was the most common site of lesions, accounting for 44.83% (13 cases). About 51.72% (15 cases) reported "no or mild" pain intensity. The median ( Q1, Q3) scores for the worst pain, duration of pain and the time to crusting of lesions in the herpes zoster cases were 3 (1.5, 5) points, 10 (1.5, 12.5) days and 10 (6.5, 13) days, respectively. There was no statistically significant difference in the constituent ratio of the location of lesions, number of lesions and pain degree among the cases with vaccination history, without vaccination history and with unknown vaccination history ( P>0.05). There was also no statistically significant difference in the distribution of pain score, duration of lesions and duration of pain across the three groups ( P>0.05). Conclusion:Wild strains are the predominant pathogens in herpes zoster cases under 20 years old in Beijing City during 2017-2021. The varicella vaccination has no significant impact on the clinical manifestations of herpes zoster cases.

Objective:To investigate the epidemiological and clinical characteristics of RSV among patients aged ≥60 years in Beijing from 2015 to 2023.Methods:Based on the respiratory pathogen surveillance system, samples of upper respiratory tract infections (URTI), non-severe community-acquired pneumonia (nsCAP) and severe community-acquired pneumonia (sCAP) among people aged ≥60 years were collected from 28 sentinel hospitals in 16 districts of Beijing from January 2015 to December 2023. Swab samples were collected from URTI within one week, and lower respiratory tract samples from nsCAP and sCAP were collected. Demographic and epidemiological data were also collected. Various respiratory pathogens including RSV were detected.Results:From January 2015 to December 2023, a total of 20 349 cases of acute respiratory infections aged ≥60 years were included, with the RSV-positive rate of 1.54% (313/20 349, 95% CI: 1.39%-1.68%). Among them, the total RSV-positive rates of older people during the pre-pandemic, pandemic, and post-pandemic periods of COVID-19 were 1.59% (207/13 006, 95% CI: 1.38%-1.81%), 0.82% (38/4 650, 95% CI: 0.56%-1.08%) and 2.53% (68/2 693, 95% CI: 1.93%-3.12%), respectively. The difference in RSV-positive rate was statistically significant ( P<0.001). Based on the sampling time of cases, the RSV epidemic season for older people in Beijing was from October to March of the following year, with a peak period in December or January of the following year. In the post COVID-19 pandemic, there were very few RSV-positive cases detected in the elderly from April to June 2023, with only one positive case detected in May and one in June. The RSV-positive rate of older people increased significantly from October to December, reaching 11.75% (51/383) in December. Among 263 RSV-positive cases in the elderly, RSV-A, RSV-B and unclassified type accounted for 43.35% (114/263), 29.28% (77/263) and 27.38% (72/263), respectively. Since 2020, there has been a subtype conversion, with RSV-B being the main focus. Among 197 elderly cases that have complete clinical data, the main symptoms were cough (86.8%, 171/197), sputum (80.2%, 158/197) and fever (73.60%, 145/197). About 24.87% (49/197) of elderly cases experienced complications. The hospitalization mortality rate was 4.57% (9/197), and the hospitalization rate was 78.68% (155/197). The ICU occupancy rate was 1.99% (36/197). The mechanical ventilation usage rate was 13.32% (33/197), and the length of hospital stay [ M ( Q1, Q3)] was 12 (9, 16) days. Conclusion:In Beijing, the RSV infection rate is relatively low during the COVID-19 pandemic, and the prevalence of COVID-19 is relatively high. In 2023, there was no out-of-season outbreak of RSV infection among the elderly. Elderly RSV infection cases have multiple complications, severe diseases, and poor prognosis.

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.